Since the first reported case of the acquired immunodeficiency syndrome (AIDS) in 1981, an estimated 5-10 million persons worldwide have become infected with human immunodeficiency virus type 1 (HlV-l) or closely related retroviruses. Rational design of an effective vaccine to stem the spread of this infection is likely to require a thorough understanding of the host immune response to these viruses. Virus specific cytotoxic T lymphocytes have been shown to play a protective role in many of viral infections. As HIV is thought to be predominantly cell associated and can be transmitted directly from cell to cell, it is possible that the cell-mediated immune response plays a critical role as a host defense in this infection. We have previously reported an assay system which facilitates the detection of HlV-l specific cytotoxic T lymphocytes (CIL). The goal of this proposal is to examine the role of HIV-specific CTL at the clonal level. HIV-l specific CTL clones will be generated by limiting dilution, using as CD3-specific monoclonal antibody aa a stimulus to proliferation. Virus specific CTL clones generated in this manner will be used to a) examine the group vs. type specificity of the HIV-l specific CIL response, b) examine the role of major histocompatibility complex (MHC) antigens in restricting HIV specific cytotoxicity. c) identify immunogenic epitopes of the virus which elicit these responses and d) generate monoclonal anti-clonotypic antibodies. These studies should help to further define the role of the cellular immune response in HlV-l infection and may be directly relevant to vaccine development.